4 个加拿大省份中抗肿瘤坏死因子 α 使用者多发性硬化症发病风险：一项基于人群的研究。
Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces: A Population-Based Study.
机构信息
From the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
出版信息
Neurology. 2023 Feb 7;100(6):e558-e567. doi: 10.1212/WNL.0000000000201472. Epub 2022 Oct 28.
BACKGROUND AND OBJECTIVES
Antitumor necrosis factor α (TNFα) agents are a class of biologic drugs used for the treatment of several immune-mediated conditions. An increased risk of multiple sclerosis (MS) with their use has been suggested, but studies have been limited. Relevant population-based epidemiologic data linking anti-TNFα to MS are scarce. The objective was to compare the risk of MS in anti-TNFα users with nonusers among patients with rheumatic disease (RD) or inflammatory bowel disease (IBD).
METHODS
A nested case-control study was conducted. Population-based health care-linked databases from 4 Canadian provinces were used. All patients with RD or IBD residing within a participating province between January 2000 and March 2018 were identified by validated case definitions. Any anti-TNFα dispensation in the 2 years before the index date (MS onset) was identified. Incident onset MS cases were ascertained using a validated algorithm. Up to 5 controls were matched to each MS case based on birth year ±3 years, disease duration, and health authority (based on region of residence). Conditional logistic regressions were used to calculate the incidence rate ratio (IRR) after adjusting for potential confounders. A meta-analysis was conducted to provide pooled estimates across provinces using random-effects models.
RESULTS
Among 296,918 patients with RD patients, 462 MS cases (80.1% female, mean [SD] age, 47.4 [14.6] years) were matched with 2,296 controls (59.5% female, mean [SD] age, 47.4 [14.5] years). Exposure to anti-TNFα occurred in 18 MS cases and 42 controls. After adjusting for matching variables, sex, and the Charlson Comorbidity Index, the pooled IRR was 2.05 (95% CI, 1.13-3.72). Among 84,458 patients with IBD, 190 MS cases (69.5% female, mean [SD] age, 44.3 [12.3] years) were matched with 943 controls (54.1% female, mean [SD] age, 44.2 [12.2] years). Exposure to anti-TNFα occurred in 23 MS cases and 98 controls. The pooled adjusted IRR was 1.35 (95% CI, 0.70-2.59).
DISCUSSION
The use of anti-TNFα was associated with an increased risk of MS compared with nonusers, especially among patients with RD. These findings could help clinicians and patients with RD to make more informed treatment decisions. Further studies are needed to validate these results for patients with IBD.
背景与目的
抗肿瘤坏死因子α（TNFα）制剂是一类用于治疗多种免疫介导疾病的生物药物。有研究提示，此类药物的使用与多发性硬化（MS）风险增加有关，但相关研究受到限制。目前，将抗 TNFα 与 MS 相关联的相关人群基于流行病学数据较为缺乏。本研究旨在比较风湿性疾病（RD）或炎症性肠病（IBD）患者中抗 TNFα 药物使用者与非使用者的 MS 风险。
方法
本研究采用巢式病例对照研究设计。使用来自加拿大 4 个省份的基于人群的医疗保健相关数据库。通过验证过的病例定义，识别出 2000 年 1 月至 2018 年 3 月期间居住在参与省份内的所有 RD 或 IBD 患者。在索引日期（MS 发病）前 2 年内确定任何抗 TNFα 药物的使用情况。通过验证过的算法确定 MS 新发病例。基于出生年份±3 年、疾病持续时间和卫生当局（基于居住地所在地区），为每个 MS 病例匹配至多 5 名对照。使用条件逻辑回归，在调整潜在混杂因素后计算发病率比（IRR）。采用随机效应模型对各省份数据进行汇总分析，提供汇总估计值。
结果
在 296918 例 RD 患者中，有 462 例 MS 病例（80.1%为女性，平均[SD]年龄为 47.4[14.6]岁）与 2296 名对照（59.5%为女性，平均[SD]年龄为 47.4[14.5]岁）相匹配。18 例 MS 病例和 42 名对照存在抗 TNFα 药物暴露情况。在调整匹配变量、性别和 Charlson 合并症指数后，汇总的 IRR 为 2.05（95%CI，1.13-3.72）。在 84458 例 IBD 患者中，有 190 例 MS 病例（69.5%为女性，平均[SD]年龄为 44.3[12.3]岁）与 943 名对照（54.1%为女性，平均[SD]年龄为 44.2[12.2]岁）相匹配。23 例 MS 病例和 98 名对照存在抗 TNFα 药物暴露情况。调整后的汇总 IRR 为 1.35（95%CI，0.70-2.59）。
讨论
与非使用者相比，抗 TNFα 药物的使用与 MS 风险增加相关，尤其是在 RD 患者中。这些发现可能有助于为 RD 患者的临床医生和患者提供更明智的治疗决策。需要进一步的研究来验证 IBD 患者的这些结果。
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